In the present research project, we have employed a combination of physiological, immunocytochemical and behavioral approaches to the study of somatosensory systems related to pain and hyperalgesia. The activity of lumbar spinal dorsal horn lamina I projection neurons was studied in normal rats and in rats with an inflammed hindpaw. Inflammation was produced by injecting Freund's adjuvant into the plantar surface 4 hours to 5 days prior to electrophysiological recording. Neurons recorded ipsilateral to the inflammation had enlarged and more complex receptive fields as compared to those observed in control rats. Many cells had high background firing rates including some bursting activity and some cells responded to joint movement in addition to cutaneous stimulation. The increased activity of this population of neurons may result in a range of pain sensations. Lamina I projection neurons were retrogradely labeled in the rat following injection of tracer into the midbrain. These neurons were shown to send their axons through the dorsolateral funiculi. A subpopulation of spinomesencephalic lamina I neurons also were retrogradely labeled from the thalamus. The neuropeptide content of long ascending projection neurons was examined by combining immunocytochemistry with retrograde tracing techniques. A small proportion of spinothalamic tract neurons, that terminate in the medial thalamus, were found to contain dynorphin or enkephalin immunoreactivity. Some cells with projections to the lateral thalamus contained cholesystokinin or vasoactive intestinal polypeptide immunoreactivity. Experiments have also been initiated to examine rat models of hyperalgesia (inflammation or nerve lesion models) using behavioral, immunocytochemical and pharmacological techniques.